Genes encoded in the I region control immune responses to many thymus-dependent antigens. The known products of these gene appear on cell surfaces as Ia antigens. The guinea pig Ia antigens are composed of alpha (33,000 m.w.) and beta (25,000 m.w.) chains. The amino terminii of the beta chains differ in amino acid sequence, but are homologous between loci within strain 13 and also between strains 13 and 2. Peptide mapping studies indicate that the guinea pig Ia alpha and beta chains appear to have large regions of very similar structure. Very little is known about the methods by which T cells control the immune response of B cells. In several systems it appears that soluble mediators are involved. In our studies on mitogen activation of lymphocytes we have found that stimulation of murine spleen and thymus cells with the pokeweed mitogen, Pa-2, causes T cells to produce a set (at least 7) of nonspecific (polyclonal) B cell stimulating or helper factors. Each of these factors causes an increase in the number of plaque forming cells in spleen cultures. At least one of these factors appears to act directly on the B cell and others require the presence of T cells for full activity.